Isotopically labeled molecules are used for structural and mechanistic studies of important chemical and biological processes. Isotopically labeled amino acids and nucleotides, for example, are used for structural and mechanistic studies of proteins and oligonucleotides. Isotopically labeled biologically active compounds, for example, are used for many phases of drug discovery and development including elucidation of biosynthetic pathways, pharmacokinetics, and drug metabolism. Compounds can be isotopically enriched with a radioactive label or with a nonradioactive label. Non-radioactive isotopes (i.e. stable isotopes) can be used to avoid subsequent disposal of radioactive waste.
Compounds labeled with stable isotopes such as carbon-13 (13C) and deuterium (2H) typically are synthesized using solution-based methods (see, for example: U.S. Pat. No. 6,730,805 to Martinez et al. entitled “Synthesis of 2H- and 13C-Substituted Compounds”; U.S. Pat. No. 6,541,671 to Martinez et al. entitled “Synthesis of [2H1, 13C], [2H2, 13C] and [2H3, 13C]Methyl Aryl Sulfides”; U.S. Pat. No. 6,713,044 to Martinez entitled “Synthesis of [2H1, 13C], [2H2, 13C] and [2H3, 13C]Methyl Aryl Sulfides”; U.S. Pat. No. 6,764,673 to Martinez et al. entitled “Synthesis of [2H1, 13C], [2H2, 13C] and [2H3, 13C]Methyl Aryl Sulfones and Sulfoxides”; U.S. Pat. No. 6,764,673; and U.S. Pat. No. 6,753,446 to Martinez et al. entitled “Synthesis of Labeled Oxalic Acid Derivatives,” all incorporated by reference herein).
Typical solution phase methods often result in product mixtures that decrease the overall yield of a desired isotopically labeled material. In addition, laborious separation and purification steps may also be needed to isolate the desired labeled material and these steps add to the cost and inefficiency of a synthesis of a desired isotopically labeled material.
The remains a need for better methods for synthesizing isotopically labeled compounds, and for compositions that can be easily converted to isotopically labeled compounds.